1. Field of the Invention
The present invention relates to an anti-histone H1 monoclonal antibody, a hybridoma for the production thereof, and a polypeptide which the anti-histone H1 antibody specifically recognizes. More specifically, the present invention relates to a monoclonal antibody, a hybridoma producing thereof, and polypeptide, which are useful for suppressing, predicting, or diagnosing transplant rejection in organ transplantation.
2. Background Technology
In organ transplantation medicine, in order to suppress transplant rejection after organ transplantation, various immunosuppressive agents have so far been used. Examples of such immunosuppressive agents include tacrolimus (FK506) and cyclosporin A (Jpn J Pharmacol, 71, 89-100, 1996). However, conventional immunosuppressive agents have problems such as strong side effects including promotion of the growth of cancer cells and suppression of bone marrow functions, infections, and need for long-lasting administration (Transplantation, 58, 170-178, 1994).
Further, it is generally difficult to assess the time to withdraw immunosuppressive agents. For example, transplanted tissue occasionally survives without continuing the administration of an immunosuppressive agent. In such cases, if the administration of an immunosuppressive agent is carelessly continued, damages simply due to its toxicity may be done to a patient. On the other hand, it is also possible that surviving tissue becomes rejected by discontinuing the administration of an immunosuppressive agent. In this case, the rejection often cannot be evaded by restarting the administration of an immunosuppressive agent.
On the other hand, various studies on organ transplantation have been carried out. For example, in the system of orthotopic liver transplantation (OLT), it has been reported that when the liver of a donor DA rat (MHC haplotype, RT1a), which has a high graft survival rate, was transplanted into a recipient PVG rat (RT1c), the graft survived without administering an immunosuppressive agent (Transplantation, 35, 304-311, 1983).
Further, it has been reported that transplant graft rejection is suppressed in a transplantation model system related to a combination which generates transplant rejection by administering once prior to operation the serum of a recipient PVG rat into which the liver of DA rat was transplanted (post-OLT serum) to the system (J. Surg. Res., 80, 56-61, 1998).
Further, it has been disclosed that transplant rejection is suppressed and a recipient survives in a heart transplantation system of a DA rat (RT1a) and a LEWIS rat (RT1l) (in vivo), which always generates transplant rejection by administering an anti-histone H1 polyclonal antibody to the system to after operation (Transplantation, 77, 1595-1603, 2004).
Further, some of the present inventors have disclosed that mixed lymphocyte reaction (MLR) is suppressed by using serum derived from a PVG rat in the early stage after transplantation and that an anti-histone H1 antibody has an MLR suppressive activity (Japanese Patent Laid-open Publication No. 2004-149507).
However, the development of a novel immunosuppressive agent which can suppress transplant rejection in organ transplantation and is excellent in safeness and its immunosuppressive activity still has been desired. Further, since it is necessary to monitor prognosis of patients or to prevent unnecessary administration of immunosuppressive agents in organ transplantation, the development of a novel drug with excellent accuracy for predicting or diagnosing the incidence of transplant rejection has also been desired.